The book covers the Shattered Legions after escaping Isstvan as they investigate a warp anomaly in the Pythos system. In particular it examines how the Iron Hands are reacting to the loss of Ferrus Manus. There's quite a bit of discussion of the different amounts of enhancement the various characters have and how strongly they're into the whole “The flesh is weak” philosophy. If you're looking for an examination of the Iron Hands and their thinking though, I'd recommend Wrath of Iron before The Damnation of Pythos any day of the week.

The Salamander and Raven Guard characters felt very much like bit parts, mainly included to make it seem slightly more plausible for the Iron Hands to not abandon the colonists to their fate. That no-one asks the colonists too many detailed questions feels to me like something of a hole in the plot. I appreciate that at this stage in the background the Loyalists don't really know the full danger of cultists and daemons and this story would serve as part of that learning process, except that no-one makes it out alive to pass the lesson on. In some ways it's a microcosm of what's happening to the Imperium at large, with the Iron Hands' effort to harness the power of the Warp backfiring horribly and the Imperial Creed spreading among the regular humans as a response to being exposed to a bit more of the darkness underlying their reality.

I think ultimately my main problem with the story is that the characters never have a chance to really affect the plot. They have no idea of what they're dealing with and no way of figuring it out. Effectively they're playing a game where they don't know the rules, so it's not much of a surprise when they lose. They do at least go down swinging, but the epilogue robs even that of any meaning. While the ship of daemons may show up later, the lack of connection to the larger story of the Heresy up to this point means the book feels like it doesn't add very much to the series. I even felt like it took something away from the Veritas Ferrum audio drama, as in the afterword David Annandale reveals it came out of writing this book and it seems like it only exists to set the scene and introduce a group of characters who are promptly bumped off.